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Peer victimization can negatively impact emotion regulation in youth and is associated with harmful mental health outcomes. One protective factor against the impacts of peer victimization is a strong attachment to family and positive peer relationships. Given that pets are commonly seen as family members and that youth report turning to their pet for emotional comfort, companion animals could provide an avenue of support for youth experiencing victimization. A geographically diverse sample of 5725 adolescents in the United States from the Adolescent Brain Cognitive Development (ABCD) Study® was used to explore whether the relationship between peer victimization and emotion regulation was moderated by whether a pet lives in the home. Having a pet in the home did not moderate the relationship between peer victimization and emotion regulation; however, mean-level differences were present across types of household pet (i.e., youth with no pets, youth with at least one dog, and youth with non-dog pets). Participants who did not live with a companion animal showed higher levels of both maladaptive emotion regulation (expressive suppression) and adaptive emotion regulation (cognitive reappraisal), suggesting that having a pet might lower overall emotion regulation pathways regardless of adaptive directionality. Relational victimization was a significant predictor of expressive suppression regardless of whether there was a pet in the home, although overt victimization was not a predictor of either kind of emotion regulation. This research demonstrates the complex nature of human-animal relationships and suggests more research is needed to understand the nuanced relationship between pets, peer victimization, and emotion regulation.
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Vítimas de Crime , Regulação Emocional , Humanos , Adolescente , Estados Unidos/epidemiologia , Animais , Cães , Animais de Estimação , Emoções , Grupo Associado , Vítimas de Crime/psicologiaRESUMO
INTRODUCTION: Relationships with companion animals have been associated with higher levels of prosocial behavior and lower levels of socioemotional difficulties for children and adolescents. Companion animals may be supportive of developing prosocial behavior in youth through practice with positive social interactions and the development of empathy and reciprocity skills. The goal of this study was to use a person-centered approach to investigate if living with a pet (including pet species) is associated with profiles of adolescent peer social behaviors (i.e., prosocial, aggressive), and size of their peer network. METHODS: This study used data from the Adolescent Brain Cognitive Development (ABCD) Study®, a large, nationally representative data set of American adolescents. RESULTS: In a cross-sectional sample of 5218 adolescents, we found that youth clustered into four different distinct profiles of peer social behavior. Female youth living with dogs were less likely to be in the High Aggression profile as compared to youth without pets or youth with other types of pets. However, having a pet was not associated with whether youth were in the profiles characterized by prosocial behaviors or size of peer network. CONCLUSIONS: Overall, future research should explore how gender intersects with companion animal interactions-both in terms of frequency of interactions as well as relationship quality/emotional attachment-as well as examine these relationships over time to assess causality.
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Comportamento do Adolescente , Animais de Estimação , Humanos , Feminino , Animais , Cães , Adolescente , Estudos Transversais , Comportamento Social , Grupo Associado , Agressão/psicologia , Comportamento do Adolescente/psicologiaRESUMO
BACKGROUND: The principle of equity is fundamental to many current debates about social issues and plays an important role in community and individual health. Traditional research has focused on singular dimensions of equity (e.g., wealth), and often lacks a comprehensive perspective. The goal of this study was to assess relationships among three domains of equity, health, wealth, and civic engagement, in a nationally representative sample of U.S. residents. METHODS: We developed a conceptual framework to guide our inquiry of equity across health, wealth, and civic engagement constructs to generate a broad but nuanced understanding of equity. Through Ipsos' KnowledgePanel service, we conducted a cross-sectional, online survey between May 29-June 20, 2020 designed to be representative of the adult U.S. POPULATION: Based on our conceptual framework, we assessed the population-weighted prevalence of health outcomes and behaviors, as well as measures of wealth and civic engagement. We linked individual-level data with population-level environmental and social context variables. Using structural equation modeling, we developed latent constructs for wealth and civic engagement, to assess associations with a measured health variable. RESULTS: We found that the distribution of sociodemographic, health, and wealth measures in our sample (n = 1267) were comparable to those from other national surveys. Our quantitative illustration of the relationships among the domains of health, wealth, and civic engagement provided support for the interrelationships of constructs within our conceptual model. Latent constructs for wealth and civic engagement were significantly correlated (p = 0.013), and both constructs were used to predict self-reported health. Beta coefficients for all indicators of health, wealth, and civic engagement had the expected direction (positive or negative associations). CONCLUSION: Through development and assessment of our comprehensive equity framework, we found significant associations among key equity domains. Our conceptual framework and results can serve as a guide for future equity research, encouraging a more thorough assessment of equity.
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Estudos Transversais , Adulto , Humanos , Inquéritos e Questionários , Estados UnidosRESUMO
The COVID-19 pandemic has resulted in significant social disruptions for youth caused by lockdowns, school closures, and a lack of in-person social interactions. Companion animals are prevalent in US households and may provide a source of emotional support and motivation for youth to engage in adaptive coping behaviors during social challenges. The goals of this study were to assess if dog owners, non-dog pet owners, and non-pet owners differed in stress levels, positive affect, and use of adaptive coping strategies such as increased time outdoors, regular walking, and healthy behaviors. This study used data collected during the COVID-19 pandemic from the Adolescent Brain Cognitive DevelopmentSM (ABCD) Study, a large, nationally representative dataset of American youth. In a cross-sectional sample of 6,069 adolescents, there were significant, but small, relationships between owning a non-dog pet and lower levels of positive affect, and both dog owners and non-dog pet owners reported higher perceived stress compared with non-pet owners. Dog ownership was associated with higher odds of using healthy coping strategies compared with non-pet owners, but this relationship was not significant when controlling for demographic variables. Dog owners reported higher odds of having a walking routine and spending time outdoors compared with non-pet owners. Overall, the results suggest no buffering effect of pet ownership on youth mental wellbeing, but dog ownership is associated with some healthy coping behaviors linked to walking.
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The idea of doing a research or scholarly project can be very daunting, however, the satisfaction of seeing a project to its completion is very rewarding. In this article, we provide medical students with guidance on whether they should take on a research or scholarly project during medical school, and how to get started, publish, and then present their project. We also highlight how such a project can benefit an applicant applying for residency training.
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Pesquisa Biomédica , Internato e Residência , Estudantes de Medicina , Humanos , Faculdades de MedicinaRESUMO
Introduction: Prenatal nicotine exposure (PNE) from maternal cigarette smoking is linked to developmental deficits, including impaired auditory processing, language, generalized intelligence, attention, and sleep. Fetal brain undergoes massive growth, organization, and connectivity during gestation, making it particularly vulnerable to neurotoxic insult. Nicotine binds to nicotinic acetylcholine receptors, which are extensively involved in growth, connectivity, and function of developing neural circuitry and neurotransmitter systems. Thus, PNE may have long-term impact on neurobehavioral development. The purpose of this study was to compare the auditory K-complex, an event-related potential reflective of auditory gating, sleep preservation and memory consolidation during sleep, in infants with and without PNE and to relate these neural correlates to neurobehavioral development. Methods: We compared brain responses to an auditory paired-click paradigm in 3- to 5-month-old infants during Stage 2 sleep, when the K-complex is best observed. We measured component amplitude and delta activity during the K-complex. Results: Infants with PNE demonstrated significantly smaller amplitude of the N550 component and reduced delta-band power within elicited K-complexes compared to nonexposed infants and also were less likely to orient with a head turn to a novel auditory stimulus (bell ring) when awake. Conclusions: PNE may impair auditory sensory gating, which may contribute to disrupted sleep and to reduced auditory discrimination and learning, attention re-orienting, and/or arousal during wakefulness reported in other studies. Implications: Links between PNE and reduced K-complex amplitude and delta power may represent altered cholinergic and GABAergic synaptic programming and possibly reflect early neural bases for PNE-linked disruptions in sleep quality and auditory processing. These may pose significant disadvantage for language acquisition, attention, and social interaction necessary for academic and social success.
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Encéfalo/efeitos dos fármacos , Fumar Cigarros/efeitos adversos , Potenciais Evocados Auditivos/efeitos dos fármacos , Nicotina/efeitos adversos , Orientação/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Estimulação Acústica/métodos , Encéfalo/fisiopatologia , Fumar Cigarros/psicologia , Fumar Cigarros/tendências , Eletroencefalografia/efeitos dos fármacos , Eletroencefalografia/métodos , Potenciais Evocados Auditivos/fisiologia , Feminino , Humanos , Lactente , Masculino , Nicotina/administração & dosagem , Orientação/fisiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/psicologiaRESUMO
Women are one of the fastest growing sectors of the prison population, and have different pathways into prison and differing needs during the reentry process when compared to men (Cloyes et al. J Forensic Nurs; 6:3-14, 2010b; Herrschaft et al. J Offender Rehabil; 48:463-482, 2009). Women report higher levels of mental health problems overall, and report more severe symptomatology (Cloyes et al. J Forensic Nurs; 6:3-14, 2010a; Hyde 2012; Lynch et al. 2014). The current study focuses on the role of severe mental disorders for women released from prison. Data collected from the North Carolina Division of Adult Correction and Juvenile Justice were used to analyze the specific role of severe mental disorders in women's recidivism at eight years post-release (n = 2311). Approximately 20% of women in this sample met the criteria for diagnosis with a severe mental disorder (SMD). Logistic regression analysis indicated that there was an association between SMDs and recidivism for this sample only (p = .11). Cox regression analyses indicated that women diagnosed with SMDs were 16% more likely to have recidivated at eight years post-release compared with women who were not diagnosed with an SMD (p < .05). Implications for the recognition, role, and treatment of SMDs during reentry are discussed.
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Transtornos Mentais/epidemiologia , Transtornos Mentais/psicologia , Prisioneiros/psicologia , Prisões , Reincidência/psicologia , Adulto , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Reincidência/estatística & dados numéricos , Estudos Retrospectivos , Fatores SexuaisRESUMO
The range of a species is determined by the balance of its demographic rates across space. Population growth rates are widely hypothesized to be greatest at the geographic center of the species range, but indirect empirical support for this pattern using abundance as a proxy has been mixed, and demographic rates are rarely quantified on a large spatial scale. Therefore, the texture of how demographic rates of a species vary over its range remains an open question. We quantified seasonal fecundity of populations spanning the majority of the global range of a single species, the saltmarsh sparrow (Ammodramus caudacutus), which demonstrates a peak of abundance at the geographic center of its range. We used a novel, population projection method to estimate seasonal fecundity inclusive of seasonal and spatial variation in life history traits that contribute to seasonal fecundity. We replicated our study over 3 years, and compared seasonal fecundity to latitude and distance among plots. We observed large-scale patterns in some life history traits that contribute to seasonal fecundity, such as an increase in clutch size with latitude. However, we observed no relationship between latitude and seasonal fecundity. Instead, fecundity varied greatly among plots separated by as little as 1 km. Our results do not support the hypothesis that demographic rates are highest at the geographic and abundance center of a species range, but rather they suggest that local drivers strongly influence saltmarsh sparrow fecundity across their global range.
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Fertilidade , Estações do Ano , Aves Canoras , Animais , Tamanho da Ninhada , DemografiaRESUMO
The balance of abiotic and biotic stressors experienced by a species likely varies across its range, resulting in spatially heterogeneous limitations on the species' demographic rates. Support for spatial variation in stressors (often latitudinal gradients) has been found in many species, usually with physiological or correlative occupancy data, but it has rarely been estimated directly with demographic data. We collected demographic data from 23 sites spanning the majority of the Saltmarsh Sparrow (Ammodramus caudacutus) breeding range. Using data from 837 nests, we quantified the abiotic and biotic variables most important to nest survival, which is the dominant driver of both fecundity and population growth rate in this species. We separately estimated daily nest failure probability due to nest depredation (biotic stressor) and nest flooding (abiotic stressor), which collectively account for almost all nest failure in the species. Nest depredation decreased with latitude, whereas nest flooding was not related to latitude. Instead, nest flooding was best predicted by a combination of maximum high tide, extremity of rare flooding events, and date. For a single vital rate, we observed predictable variation in competing biotic and abiotic stressors across this species range. We observed that biotic and abiotic stressors were geographically independent, both on a large spatial scale and locally. Our results suggest that stressors on the fecundity of Saltmarsh Sparrow vary systematically across its range, but independently. The observed patterns of biotic and abiotic stress provide information for efforts to conserve the Saltmarsh Sparrow, which is considered threatened. Further, understanding the effects that different stressors, and their interactions, have on demographic rates is necessary to unravel the processes that govern species distributions and to effectively conserve biodiversity in the face of global change.
El balance de factores de estrés abióticos y bióticos para una especie probablemente varía a través de su rango, dando como resultado limitaciones espaciales heterogéneas en las tasas demográficas de la especie. Se ha verificado la existencia de variación espacial en los factores de estrés (usualmente gradientes latitudinales) para muchas especies, usualmente con datos fisiológicos o de ocupación correlativa, pero raramente se ha estimado directamente con datos demográficos. Colectamos datos demográficos de 23 sitios abarcando la mayoría del rango reproductivo de Ammodramus caudacutus. Usando datos de 837 nidos, cuantificamos las variables abióticas y bióticas más importantes para la supervivencia del nido, que es la variable que determina tanto la fecundidad como la tasa de crecimiento poblacional en esta especie. Por otra parte, estimamos la probabilidad de fracaso diario del nido debido a la depredación del nido (factor de estrés biótico) e inundación del nido (factor de estrés abiótico), que juntos representaron casi todos los fracasos del nido en esta especie. La depredación del nido disminuyó con la latitud mientras que la inundación del nido no se relacionó con la latitud. En cambio, la inundación del nido se predijo mejor por una combinación del máximo superior de la marea, la extremidad de los eventos de inundación raros y la fecha. Considerando una sola tasa vital, observamos variación predecible en los factores de estrés biótico y abiótico que compiten a través del rango de la especie. Observamos que los factores de estrés biótico y abiótico fueron geográficamente independientes tanto a una escala espacial grande como a la escala local. Nuestros resultados sugieren que los factores de estrés relacionados a la fecundidad de A. caudacutus varían sistemática pero independientemente a través de su rango. Los patrones observados de estrés biótico y abiótico brindan información para los esfuerzos de conservación de A. caudacutus, una especie considerada amenazada. Más aún, es necesario entender los efectos que los diferentes factores de estrés y sus interacciones tienen en las tasas demográficas para desenmarañar los procesos que gobiernan las distribuciones de las especies y para conservar la biodiversidad de manera eficiente en miras al cambio global.
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An 8-yr-old, captive, female golden lion tamarin ( Leontopithecus rosalia ) with a 6-yr history of hyperbilirubinemia was examined for inappetence and weight loss. Physical examination and blood pressure monitoring under anesthesia revealed hypothermia and hypotension, and blood work revealed hypoglycemia, markedly elevated liver enzymes, including serum alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase, and confirmed the hyperbilirubinemia. A complete blood count suggested chronic lymphoid leukemia. The animal's condition deteriorated during recovery, and the animal died despite aggressive treatment. Grossly, there was micronodular cirrhosis of the liver, severe icterus, and diffuse osteopenia of all examined bones. Microscopic examination of the liver confirmed the micronodular cirrhosis and bone lesions were compatible with diffuse osteopenia and osteomalacia. This brief communication presents a case of chronic liver disease and lesions indicative of metabolic bone disease, also known as hepatic osteodystrophy. To the authors' knowledge, this is the first documented case of hepatic osteodystrophy in the veterinary literature.
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Doenças Ósseas Metabólicas/veterinária , Leontopithecus , Hepatopatias/veterinária , Doenças dos Macacos/patologia , Animais , Doenças Ósseas Metabólicas/patologia , Evolução Fatal , Feminino , Hepatopatias/patologiaRESUMO
BACKGROUND: The mechanisms of paraneoplastic thrombocytosis in ovarian cancer and the role that platelets play in abetting cancer growth are unclear. METHODS: We analyzed clinical data on 619 patients with epithelial ovarian cancer to test associations between platelet counts and disease outcome. Human samples and mouse models of epithelial ovarian cancer were used to explore the underlying mechanisms of paraneoplastic thrombocytosis. The effects of platelets on tumor growth and angiogenesis were ascertained. RESULTS: Thrombocytosis was significantly associated with advanced disease and shortened survival. Plasma levels of thrombopoietin and interleukin-6 were significantly elevated in patients who had thrombocytosis as compared with those who did not. In mouse models, increased hepatic thrombopoietin synthesis in response to tumor-derived interleukin-6 was an underlying mechanism of paraneoplastic thrombocytosis. Tumor-derived interleukin-6 and hepatic thrombopoietin were also linked to thrombocytosis in patients. Silencing thrombopoietin and interleukin-6 abrogated thrombocytosis in tumor-bearing mice. Anti-interleukin-6 antibody treatment significantly reduced platelet counts in tumor-bearing mice and in patients with epithelial ovarian cancer. In addition, neutralizing interleukin-6 significantly enhanced the therapeutic efficacy of paclitaxel in mouse models of epithelial ovarian cancer. The use of an antiplatelet antibody to halve platelet counts in tumor-bearing mice significantly reduced tumor growth and angiogenesis. CONCLUSIONS: These findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplastic thrombocytosis, which fuels tumor growth. We speculate that countering paraneoplastic thrombocytosis either directly or indirectly by targeting these cytokines may have therapeutic potential. (Funded by the National Cancer Institute and others.).
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Interleucina-6/antagonistas & inibidores , Neoplasias Epiteliais e Glandulares/complicações , Neoplasias Ovarianas/complicações , Síndromes Paraneoplásicas , Trombocitose/etiologia , Animais , Anticorpos Monoclonais/uso terapêutico , Plaquetas/imunologia , Modelos Animais de Doenças , Intervalo Livre de Doença , Feminino , Humanos , Interleucina-6/sangue , Interleucina-6/imunologia , Estimativa de Kaplan-Meier , Camundongos , Camundongos Knockout , Neoplasias Epiteliais e Glandulares/sangue , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/tratamento farmacológico , Contagem de Plaquetas , Modelos de Riscos Proporcionais , Receptores de Interleucina-6/deficiência , Transdução de Sinais , Trombopoetina/antagonistas & inibidores , Trombopoetina/sangueRESUMO
Pet acquisition purportedly increased during the COVID-19 pandemic with individuals acquiring pets during periods of social isolation. Families with children experienced unique challenges during the COVID-19 pandemic, balancing childcare, remote schooling, and other needs and therefore patterns of pet acquisition and loss may differ from the broader population. The goal of this study was to understand patterns of pet ownership within families with adolescents during the pandemic to help identify areas for improved support and programmatic recommendations. Using self-reported survey data from a sample of 7,590 American adolescents from the Adolescent Brain Cognitive Development (ABCD) Study® COVID Survey, we found no evidence for large-scale changes in pet acquisition or relinquishment during the first year of the pandemic for families with adolescents in the U.S. Future research should explore the effects of pet acquisition and pet loss on families with adolescents and what resources are needed to support pet ownership during stressors such as the COVID-19 pandemic.
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Firefighters are trained to respond to a wide range of emergencies, and over the course of responding to emergencies, are exposed to a variety of potentially traumatic events. Repeated exposure to traumatic events may adversely impact firefighters' mental health. Combined with stigma surrounding help-seeking, lack of systematic resources and referral programs, and other barriers to care, firefighters do not routinely receive a continuum of trauma informed, assessment and treatment services from trained professionals. The purpose of this paper is to describe an evidence-informed approach to a reciprocal, collaborative model among social work and public health practice, policy, and research; and to offer a framework for researchers, clinicians, and policy advocates to more effectively achieve goals of preventing and treating trauma exposure in firefighters. This paper provides a comprehensive literature review, as well as describes a case study of a successful public health intervention for mitigating exposure to trauma among a population of firefighters. The significant contribution of mental health issues to the burden of disease among our firefighters is a matter of considerable public health concern. Effective approaches to mitigating behavioral health needs must bridge both mental health disciplines and public health to minimally, include access to evidence-based assessment and treatment, peer support capacity building, widely available mental health education, and leadership development to promote culture change. When considering a model for services with firefighters, reciprocal collaboration among researchers, health care professionals, first responder organizations, families, and other relevant community stakeholders is essential for success.
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Saúde Mental , Saúde Pública , Humanos , Emergências , Serviço SocialRESUMO
OBJECTIVE: The objective of this study is to investigate whether wild-type TP53 status in high-grade serous ovarian carcinoma is associated with poorer survival. METHODS: Clinical and genomic data of 316 sequenced samples from The Cancer Genome Atlas (TCGA) ovarian high-grade serous carcinoma study were downloaded from TCGA data portal. Association between wild-type TP53 and survival was analyzed with Kaplan Meier method and Cox regression. The diagnosis of high-grade serous carcinomas was evaluated by reviewing pathological reports and high-resolution hematoxylin and eosin (H&E) images from frozen sections. The authenticity of wild-type TP53 in these tumor samples was assessed by analyzing SNP array data with ASCAT algorithm, reverse phase protein array (RPPA) data and RNAseq data. RESULTS: Fifteen patients with high grade serous ovarian carcinomas were identified to have wild-type TP53, which had significantly shorter survival and higher chemoresistance than those with mutated TP53. The authenticity of wild-type TP53 status in these fifteen patients was supported by SNP array, RPPA, and RNAseq data. Except four cases with mixed histology, the classification as high grade serous carcinomas was supported by pathological reports and H&E images. Using RNAseq data, it was found that EDA2R gene, a direct target of wild-type TP53, was highly up-regulated in samples with wild-type TP53 in comparison to samples with either nonsense or missense TP53 mutations. CONCLUSION: Although patients with wild-type TP53 ovarian cancer were rare in the TCGA high grade ovarian serous carcinomas cohort, these patients appeared to have a poorer survival and were more chemoresistant than those with mutated TP53. Differentially expressed genes in these TP53 wild-type tumors may provide insight in the molecular mechanism in chemotherapy resistance.
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Cistadenocarcinoma Seroso/genética , Regulação Neoplásica da Expressão Gênica/genética , Genes p53/genética , Neoplasias Ovarianas/genética , Receptor Xedar/genética , Cistadenocarcinoma Seroso/patologia , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Ovarianas/patologia , Polimorfismo de Nucleotídeo Único , Modelos de Riscos Proporcionais , Análise Serial de Proteínas , Análise de Sequência de RNA , Regulação para CimaRESUMO
PAX2 is one of nine PAX genes that regulate tissue development and cellular differentiation in embryos. However, the functional role of PAX2 in ovarian cancer is not known. Twenty-six ovarian cancer cell lines with different histology origins were screened for PAX2 expression. Two ovarian cancer cell lines: RMUGL (mucinous) and TOV21G (clear cell), with high PAX2 expression were chosen for further study. Knockdown PAX2 expression in these cell lines was achieved by lentiviral shRNAs targeting the PAX2 gene. PAX2 stable knockdown cells were characterized for cell proliferation, migration, apoptosis, protein profiles, and gene expression profiles. The result indicated that these stable PAX2 knockdown cells had reduced cell proliferation and migration. Microarray analysis indicated that several genes involved in growth inhibition and motility, such as G0S2, GREM1, and WFDC1, were up-regulated in PAX2 knockdown cells. On the other hand, over-expressing PAX2 in PAX2-negative ovarian cell lines suppressed their cell proliferation. In summary, PAX2 could have both oncogenic and tumor suppression functions, which might depend on the genetic content of the ovarian cancer cells. Further investigation of PAX2 in tumor suppression and mortality is warranty.
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Stroke is a leading cause of disability worldwide and upper limb hemiparesis is the most common post-stroke disability. Recent studies suggest that clinically significant motor recovery is possible in chronic stroke survivors with severe impairment of the upper limb. Three promising strategies that have been investigated are (1) high dose rehabilitation therapy (2) bilateral motor priming and (3) vagus nerve stimulation. We propose that the future of effective and efficient upper limb rehabilitation will likely require a combination of these approaches.
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Phase separation plays crucial roles in both sustaining cellular function and perpetuating disease states. Despite extensive studies, our understanding of this process is hindered by low solubility of phase-separating proteins. One example of this is found in SR and SR-related proteins. These proteins are characterized by domains rich in arginine and serine (RS domains), which are essential to alternative splicing and in vivo phase separation. However, they are also responsible for a low solubility that has made these proteins difficult to study for decades. Here, we solubilize the founding member of the SR family, SRSF1, by introducing a peptide mimicking RS repeats as a co-solute. We find that this RS-mimic peptide forms interactions similar to those of the protein's RS domain. Both interact with a combination of surface-exposed aromatic residues and acidic residues on SRSF1's RNA Recognition Motifs (RRMs) through electrostatic and cation-pi interactions. Analysis of RRM domains from human SR proteins indicates that these sites are conserved across the protein family. In addition to opening an avenue to previously unavailable proteins, our work provides insight into how SR proteins phase separate and participate in nuclear speckles.
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Processamento Alternativo , Proteínas Nucleares , Humanos , Fosforilação , Eletricidade Estática , Proteínas Nucleares/metabolismo , Peptídeos/metabolismo , Arginina/metabolismo , Splicing de RNA , Serina/metabolismo , Fatores de Processamento de Serina-Arginina/genética , Fatores de Processamento de Serina-Arginina/metabolismoRESUMO
BACKGROUND: The objective of the study was to determine if initial surgery (IS) or initial chemotherapy (IC) affects rates of optimal surgery and survival in a population with significant medical comorbidities. METHODS: Data of all patients with stage III-IV ovarian, peritoneal, and fallopian tube cancers diagnosed from 1995 to 2008 were reviewed. Clinical and pathologic data were abstracted. RESULTS: There were 551 cases for review: 255 (46.3%) received IS, and 296 (53.7%) received IC. Patients who received IC had higher stage (P < 0.001), higher-grade cancers (P < 0.001), higher mean CA-125 (P = 0.015), higher rates of diabetes (P = 0.006), hypertension (P = 0.008), and presurgical embolism (P < 0.022) and were older (P = 0.043). There was no difference with respect to body mass index, albumin, extent of surgery, or intensive care use. Rates of optimal cytoreduction were higher with IC compared with IS (72.7% vs 56.1%, P < 0.001). IS was associated with more blood loss (P = 0.005) and higher rates of postsurgical venous thrombosis (P < 0.001). Optimal cytoreduction predicted survival in both groups. Among optimal patients, IS improved median survival: progression-free survival of 14 months (IS) versus 12 months (IC), P = 0.004; overall survival of 58 months (IS) versus 34 months (IC), P = 0.002. Factors influencing this difference were receipt of IC and history of diabetes; both predictors of mortality: hazard ratios, 1.9 (95% confidence interval, 1.3-2.8; P < 0.001) and 1.8 (95% confidence interval, 1.02-3.1; P = 0.042), respectively. CONCLUSIONS: The achievement of optimal cytoreduction continues to be a significant predictor of survival, regardless of treatment approach. Patients selected for IS and in whom optimal cytoreduction was achieved had improvements in both progression-free survival and overall survival. However, the differences could not be explained by surgical effort alone as diabetes was independently associated with mortality.
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Neoplasias das Tubas Uterinas/mortalidade , Neoplasias das Tubas Uterinas/cirurgia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/cirurgia , Antígeno Ca-125/metabolismo , Comorbidade , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Prognóstico , Taxa de SobrevidaRESUMO
Learning to sequence movements is necessary for skillful interaction with the environment. Neuroplasticity, particularly long-term potentiation (LTP), within sensorimotor networks underlies the acquisition of motor skill. Short-term immobilization of the arm, even less than 12 hours, can reduce corticospinal excitability and increase the capacity for LTP-like plasticity within the contralateral primary motor cortex. However, it is still unclear whether short-term immobilization influences motor skill acquisition. The current study aimed to evaluate the effect of short-term arm immobilization on implicit, sequence-specific motor skill acquisition using a modified Serial Reaction Time Task (SRTT). Twenty young, neurotypical adults underwent a single SRTT training session after six hours of immobilization of the non-dominant arm or an equivalent period of no immobilization. Our results demonstrated that participants improved SRTT performance overall after training, but there was no evidence of an effect of immobilization prior to task training on performance improvement. Further, improvements on the SRTT were not sequence-specific. Taken together, motor skill acquisition for sequential, individuated finger movements improved following training but the effect of six hours of immobilization was difficult to discern.